Probiotics alleviate maternal metabolic disorders and offspring-islet abnormalities in gestational diabetic mice

Abstract

• The islets of the GDM offspring mice show a “pre-mature” state at birth. • BiLaEn can avoid the excessive development of islets in GDM offspring mice. • The mTORC1 signaling in islets of GDM mice is not synchronized with normal. Gestational diabetes mellitus (GDM) amplifies the intergenerational risk for early-onset metabolic diseases in offspring, yet the pathogenesis remains unclear. We investigated the impacts of GDM on islets development and maturation in offspring mice and whether probiotics (BiLaEn) have protective effects. Strikingly, GDM caused abnormal prenatal development of islets in offspring mice, with abnormally high-expression insulin and glucagon at birth, showing premature or quasi-mature state; the process of β-cell maturation and mTORC1 signalling were not synchronized with normal offspring mice within 14 days after birth. Furthermore, BiLaEn treatment benefited the normal development and maturation of GDM-offspring islets, avoiding “quasi-mature” at birth, which were based on the improvement of intestinal flora disturbance and leaky gut in GDM maternal mice. These data highlight the premature development of GDM-offspring islets as potential cause of early-onset metabolic diseases in GDM offspring, and targeted regulation of intestinal flora is expected to be safe and effective intervention.